The Candidate proposes this Mentored Patient-Oriented Research Career Award application to provide her with expert training and mentorship to support her development as an independent clinician scientist in the field of perinatal mental health. The long-term career goals of the Candidate are 1) To establish a program of research focusing on the treatment and predictors of treatment response for major psychiatric disorders in pregnant women; 2) To develop the translational aspects of her clinical research program by fully incorporating a sophisticated understanding of the neuroendocrinology of pregnancy; 3) To develop her skills as an independent investigator, educator and mentor focusing on patient-oriented research at the interface between psychiatry and obstetrics and gynecology. In order to meet these goals, the application provides a detailed description of 5 training modules including 1) Research projects, 2) Laboratory training, 3) Didactic course work including completion of a Masters in Translational Research, 4) Individual tutorials, and 5) Extramural supervision. The development of researchers focused on the treatment of depression during pregnancy has important ramifications for mother and her offspring. Depression during pregnancy affects approximately 13% of pregnant women making it a national health issue of vital importance. There is mounting evidence that antidepressants may adversely affect pregnancy outcome and fetal health. Psychotherapy is a first-line treatment for this special population but other options must be studied as no treatment will work in all patients. Repetitive transcranial magnetic stimulation (rTMS) is a FDA-approved device for the non-pharmacologic treatment of depression in adults. It is critical that rTMS, as a non-pharmacologic treatment, be evaluated for the treatment of major depressive disorder (MDD) during pregnancy. Our pilot data suggests this is a feasible and safe treatment for 2nd and 3rd trimester pregnant women with depression. Our pilot data also suggests that the device parameters may be affected by the pregnant state which if not addressed could affect efficacy. We propose a double-blind, placebo-controlled clinical trial using 1 Hz active versus sham rTMS of the right dorsolateral prefrontal cortex (DLPFC) of 66 pregnant women with moderate to severe major depressive disorder (MDD). We expect a significant decrease in depression scores after 20 sessions in the active group compared to the sham group. In addition, we will evaluate the device power output necessary to obtain the resting motor threshold in pregnant subjects compared to 16 age-matched, non-pregnant, healthy women in the luteal phase of the menstrual cycle. Finally, to better understand the mechanism by which rTMS may be effective for the treatment of depression during pregnancy, we will measure maternal serum brain derived neurotrophic factor (BDNF) and correlate it with levels of estradiol, progesterone, allopregnanolone, oxytocin and corticotrophin-releasing hormone (CRH) levels pre and post-rTMS. This award will solidly prepare the Candidate to pursue further research funding and the development of non-pharmacological, somatic treatments for pregnant women suffering from mental illness. PUBLIC HEALTH RELEVANCE: Depression during pregnancy is a common illness that affects both mother and child. Many women prefer not to take antidepressant medications during pregnancy. We will study a non- medication, somatic alternative called repetitive transcranial magnetic stimulation (rTMS) which could provide pregnant women with depression an alternative treatment option.